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Single‐cell high‐content imaging parameters predict functional phenotype of cultured human bone marrow stromal stem cells
Author(s) -
Kowal Justyna M.,
Schmal Hagen,
Halekoh Ulrich,
Hjelmborg Jacob B.,
Kassem Moustapha
Publication year - 2020
Publication title -
stem cells translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.781
H-Index - 71
eISSN - 2157-6580
pISSN - 2157-6564
DOI - 10.1002/sctm.19-0171
Subject(s) - mesenchymal stem cell , microbiology and biotechnology , stem cell , stromal cell , cell , bone marrow , in vivo , cellular differentiation , biology , cell culture , chemistry , pathology , cancer research , immunology , medicine , biochemistry , genetics , gene
Cultured human bone marrow stromal (mesenchymal) stem cells (hBM‐MSCs) are heterogenous cell populations exhibiting variable biological properties. Quantitative high‐content imaging technology allows identification of morphological markers at a single cell resolution that are determinant for cellular functions. We determined the morphological characteristics of cultured primary hBM‐MSCs and examined their predictive value for hBM‐MSC functionality. BM‐MSCs were isolated from 56 donors and characterized for their proliferative and differentiation potential. We correlated these data with cellular and nuclear morphological features determined by Operetta; a high‐content imaging system. Cell area, cell geometry, and nucleus geometry of cultured hBM‐MSCs exhibited significant correlation with expression of hBM‐MSC membrane markers: ALP, CD146, and CD271. Proliferation capacity correlated negatively with cell and nucleus area and positively with cytoskeleton texture features. In addition, in vitro differentiation to osteoblasts as well as in vivo heterotopic bone formation was associated with decreased ratio of nucleus width to length. Multivariable analysis applying a stability selection procedure identified nuclear geometry and texture as predictors for hBM‐MSCs differentiation potential to osteoblasts or adipocytes. Our data demonstrate that by employing a limited number of cell morphological characteristics, it is possible to predict the functional phenotype of cultured hBM‐MSCs and thus can be used as a screening test for “quality” of hBM‐MSCs prior their use in clinical protocols.

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